Endothelium-Mediated Dilations Contribute to the Polarity of the Arterial Wall in Vasomotion Induced by α2-Adrenergic Agonists

Abstract
We tested whether or not an endothelium-me-diated dilation is involved in the response of intact arteries to a-adrenergic stimulation, by separately applying agonists to the luminal or adventitial side of the arterial wall. Cumulative dose-response curves of the α1-ago-nists l-phenylephrine or cirazoline applied luminally in rat tail arteries and in side branches of canine femoral arteries were identical to those obtained by adventitial application in the intact arteries, and were not modified by removal of the endothelium (eliminating acetylcholine-induced dilations). Constrictions induced by the α2-agonists UK-14,304 or azepexole applied luminally were significantly lower than those induced by adventitial application, and were augmented significantly by removal of the endothelium. Half-maximally precontracted arteries were dilated by addition of α2-agonists to the luminal perfusate; these dilations were abolished by removal of the endothelium. It is concluded that the functional polarity of the vascular wall of these arteries in response to α2-agonists results from the release of a dilatory signal from the endothelial cells, counteracting the direct contractile activation of the adjacent smooth muscle cells by the agonists.